2527-66-4Relevant articles and documents
Synthesis method of N-alkane-1, 2-benzisothiazoline-3-ketone
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Paragraph 0039-0041, (2021/04/10)
The invention discloses a synthetic method of N-alkane-1,2-benzisothiazoline-3-ketone, which comprises the following steps: (1) under the protection of nitrogen, mixing and stirring phenyl sulfur chloride and a solvent; (2) dropwise adding alkyl carbamyl chloride; (3) slowly heating until hydrogen chloride is released and the system becomes turbid from clear and then becomes clear again; (4) mixing and stirring a catalyst and the solvent, keeping the temperature, and dropwise adding the mixture; (5) after dropwise adding, heating the system to 90 DEG C, keeping the temperature for 2 hours, and detecting that the BIT intermediate residue is less than 0.5% by HPLC; and (6) cooling to 30-40 DEG C, adding water while stirring, standing for layering, and carrying out reduced pressure distillation on the upper organic layer to obtain the N-alkane 1, 2-benzisothiazoline-3-ketone. The method has the advantages of cheap raw materials, low process difficulty, simple process flow, less wastewater amount, high yield, less solid waste, environmental friendliness and the like.
Benzisothiazolinone Derivatives as Potent Allosteric Monoacylglycerol Lipase Inhibitors That Functionally Mimic Sulfenylation of Regulatory Cysteines
Castelli, Riccardo,Scalvini, Laura,Vacondio, Federica,Lodola, Alessio,Anselmi, Mattia,Vezzosi, Stefano,Carmi, Caterina,Bassi, Michele,Ferlenghi, Francesca,Rivara, Silvia,M?ller, Ingvar R.,Rand, Kasper D.,Daglian, Jennifer,Wei, Don,Dotsey, Emmanuel Y.,Ahmed, Faizy,Jung, Kwang-Mook,Stella, Nephi,Singh, Simar,Mor, Marco,Piomelli, Daniele
, p. 1261 - 1280 (2019/12/25)
We describe a set of benzisothiazolinone (BTZ) derivatives that are potent inhibitors of monoacylglycerol lipase (MGL), the primary degrading enzyme for the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG). Structure-activity relationship studies evaluated various substitutions on the nitrogen atom and the benzene ring of the BTZ nucleus. Optimized derivatives with nanomolar potency allowed us to investigate the mechanism of MGL inhibition. Site-directed mutagenesis and mass spectrometry experiments showed that BTZs interact in a covalent reversible manner with regulatory cysteines, Cys201 and Cys208, causing a reversible sulfenylation known to modulate MGL activity. Metadynamics simulations revealed that BTZ adducts favor a closed conformation of MGL that occludes substrate recruitment. The BTZ derivative 13 protected neuronal cells from oxidative stimuli and increased 2-AG levels in the mouse brain. The results identify Cys201 and Cys208 as key regulators of MGL function and point to the BTZ scaffold as a useful starting point for the discovery of allosteric MGL inhibitors.
Pipeline type continuous production method of 3-isothiazolinone compound
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Paragraph 0023, (2019/12/02)
The invention discloses a pipeline type continuous production method of a 3-isothiazolinone compound, which comprises the following steps: carrying out mixed reaction on a thioamide compound, a catalyst, a solvent and chlorine through a pipeline reactor system, and carrying out after-treatment after the reaction is completed to obtain the 3-isothiazolinone compound. According to the method, the defects of large occupied area, small productivity, low efficiency, high energy consumption and small safety coefficient caused by existing batch production of the 3-isothiazolinone compound are overcome; the invention provides a mode for continuously producing the 3-isothiazolinone compound, so that the reaction process is easy to control, energy consumption is reduced, the production efficiency and the safety coefficient of the production process are improved, and the process is an efficient and energy-saving safe production process.
